A Positron Emission Tomography Radioligand for the in Vivo Labeling of Metabotropic Glutamate 1 Receptor:  (3-Ethyl-2-[<sup>11</sup>C]methyl-6-quinolinyl)(<i>cis</i>- 4-methoxycyclohexyl)methanone

Huang, Yiyun; Narendran, Raj; Bischoff, François; Guo, Ningning; Zhu, Zhihong; Bae, Sua; Lesage, and Anne S.; Laruelle, Marc

doi:10.1021/jm050263+

Cited by 47 publications

(40 citation statements)

References 15 publications

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“…Moreover, these uptakes were significantly decreased by pretreatment with mGluR1-selective JNJ16259685 and were not affected by pretreatment with mGluR5-selective MPEP. In baseline PET, the uptake ratio of the mGluR1-richest cerebellum to the mGluR1-poorest pons was roughly 11 for [ 18 [9,12]. The binding affinities for mGluR1 are also similar for both ligands.…”

Section: Discussionmentioning

confidence: 99%

“…To image mGluR1 in vivo, a number of positron emission tomography (PET) ligands such as [ 11 C]JNJ-16567083 [9], [ 18 F]FTIDC [10], [ 11 C]YM-202074 [11], [ 18 F]MK-1312 [12], [ 11 C]MMTP [13], [ 18 F]FPIT [14] and [ 18 F]FTPQ [15] have been synthesized. Among these, [ 18 F] MK-1312, [ 18 F]FPIT and [ 11 C]MMTP have been used for monkey PET.…”

Section: Introductionmentioning

confidence: 99%

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Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [18F]FITM

Yamasaki

Fujinaga²,

Maeda³

et al. 2011

Eur J Nucl Med Mol Imaging

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Purpose In this study, we evaluate the utility of 4-[ 18 F]fluoro-N- [4-[6-(isopropylamino)pyrimidin-4-yl]-1,3-thiazol-2-yl]-Nmethylbenzamide ([ 18 F]FITM) as a positron emission tomography (PET) ligand for imaging of the metabotropic glutamate receptor subtype 1 (mGluR1) in rat and monkey brains. Methods In vivo distribution of [ 18 F]FITM in brains was evaluated by PET scans with or without the mGluR1-selective antagonist (JNJ16259685). Kinetic parameters of monkey PET data were obtained using the two-tissue compartment model with arterial blood sampling. Results In PET studies in rat and monkey brains, the highest uptake of radioactivity was in the cerebellum, followed by moderate uptake in the thalamus, hippocampus and striatum. The lowest uptake of radioactivity was detected in the pons. These uptakes in all brain regions were dramatically decreased by pre-administration of JNJ16259685. In kinetic analysis of monkey PET, the highest volume of distribution (V T ) was detected in the cerebellum (V T =11.5). Conclusion [ 18 F]FITM has an excellent profile as a PET ligand for mGluR1 imaging. PET with [ 18 F]FITM may prove useful for determining the regional distribution and density of mGluR1 and the mGluR1 occupancy of drugs in human brains.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [18F]FITM

Yamasaki

Fujinaga²,

Maeda³

et al. 2011

Eur J Nucl Med Mol Imaging

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“…Therefore, in vivo imaging of mGluR1 may provide crucial information about its functions in the living human brain under healthy and pathologic conditions and facilitate the development of CNS drugs targeting mGluR1. Several groups have developed radiotracers for selective imaging of mGluR1 in the human brain by PET (12)(13)(14)(15)(16)(17)(18)(19)(20). Despite these efforts, there have been no clinical studies using radioligands for mGluR1 in the human brain.…”

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confidence: 99%

Initial Human PET Studies of Metabotropic Glutamate Receptor Type 1 Ligand ¹¹C-ITMM

et al. 2013

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( 11 C-ITMM) is a potential radioligand for mapping metabotropic glutamate receptor type 1 (mGluR1) in the brain by PET. The present study was performed to determine the safety, distribution, radiation dosimetry, and initial brain imaging of 11 C-ITMM in healthy human subjects. Methods: The multiorgan biodistribution and radiation dosimetry of 11 C-ITMM were assessed in 3 healthy human subjects, who underwent 2-h whole-body PET scans. Radiation dosimetry was estimated from the normalized number of disintegrations of source organs using the OLINDA/EXM program. Five healthy human subjects underwent 90-min dynamic 11 C-ITMM scans of brain regions with arterial blood sampling. For anatomic coregistration, T1-weighted MR imaging was performed. Metabolites in plasma and urine samples were analyzed by high-performance liquid chromatography. 11 C-ITMM uptake was assessed quantitatively using a 2-tissue-compartment model. Results: There were no serious adverse events in any of the subjects throughout the study period. 11 C-ITMM PET demonstrated high uptake in the urinary bladder and gallbladder, indicating both urinary and fecal excretion of radioactivity. The absorbed dose (mGy/MBq) was highest in the urinary bladder wall (13.2 6 3.5), small intestine (9.8 6 1.7), and liver (9.1 6 2.0). The estimated effective dose for 11 C-ITMM was 4.6 6 0.3 mSv/MBq. 11 C-ITMM showed a gradual increase of radioactivity in the cerebellar cortex. The total distribution volume in the brain regions ranged from 2.61 6 0.30 (cerebellar cortex) to 0.52 6 0.17 (pons), and the rank order of the corresponding total distribution volume of 11 C-ITMM was cerebellar cortex . thalamus . frontal cortex . striatum pons, which was consistent with the known distribution of mGluR1 in the primate brain. The rate of 11 C-ITMM metabolism in plasma was moderate: at 60 min after injection, 62.2% 6 8.2% of the radioactivity in plasma was intact parent compound. Conclusion: The initial findings of the present study indicated that 11 C-ITMM PET is feasible for imaging of mGluR1 in the brain. The low effective dose will permit serial examinations in the same subjects.

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“…Increased knowledge concerning the connection between PSMA folate hydrolase activity and glutamate signaling in both prostate tumors and in neoangiogenesis would also be helpful in terms of drug development, diagnostic and prognostic significance. Radiolabeled small molecule probes for the NMDAR [76], mGluR5 [77–82] and mGluR1 [83–85] have been developed to allow patient selection for targeted therapies to augment or disrupt interactions between these proteins. Radiolabeled small molecule probes targeting PSMA for positron emission tomography (PET) and single photon emission computed tomography (SPECT) imaging have also been developed and will be described in the following sections.…”

Section: Psma In Cancermentioning

confidence: 99%

GCPII Imaging and Cancer

Foss¹,

Mease²,

Cho³

et al. 2012

CMC

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Glutamate carboxypeptidase II (GCPII) in the central nervous system is referred to as the prostate-specific membrane antigen (PSMA) in the periphery. PSMA serves as a target for imaging and treatment of prostate cancer and because of its expression in solid tumor neovasculature has the potential to be used in this regard for other malignancies as well. An overview of GCPII/PSMA in cancer, as well as a discussion of imaging and therapy of prostate cancer using a wide variety of PSMA-targeting agents is provided.

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A Positron Emission Tomography Radioligand for the in Vivo Labeling of Metabotropic Glutamate 1 Receptor: (3-Ethyl-2-[¹¹C]methyl-6-quinolinyl)(cis- 4-methoxycyclohexyl)methanone

Cited by 47 publications

References 15 publications

Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [18F]FITM

Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [18F]FITM

Initial Human PET Studies of Metabotropic Glutamate Receptor Type 1 Ligand ¹¹C-ITMM

GCPII Imaging and Cancer

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A Positron Emission Tomography Radioligand for the in Vivo Labeling of Metabotropic Glutamate 1 Receptor: (3-Ethyl-2-[11C]methyl-6-quinolinyl)(cis- 4-methoxycyclohexyl)methanone

Cited by 47 publications

References 15 publications

Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [18F]FITM

Imaging for metabotropic glutamate receptor subtype 1 in rat and monkey brains using PET with [18F]FITM

Initial Human PET Studies of Metabotropic Glutamate Receptor Type 1 Ligand 11C-ITMM

GCPII Imaging and Cancer

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Resources

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A Positron Emission Tomography Radioligand for the in Vivo Labeling of Metabotropic Glutamate 1 Receptor: (3-Ethyl-2-[¹¹C]methyl-6-quinolinyl)(cis- 4-methoxycyclohexyl)methanone

Initial Human PET Studies of Metabotropic Glutamate Receptor Type 1 Ligand ¹¹C-ITMM